Brain cancer diagnosis requires histological, molecular, and genomic tumor analyses. Since conventional imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) don’t provide molecular characterisation, tumor sampling is often achieved using a targeted needle biopsy approach. Targeting errors and cancer heterogeneity are important limitations of this technique, causing inaccurate sampling resulting in non-diagnostic or poor quality samples leading and the need for repeated biopsies, which poses an elevated patient risk because of infections and potential hemorrhages. Previously, we presented the design of an optically-guided brain biopsy needle using high wavenumber Raman spectroscopy (RS) to characterize tissue prior to sample collection with demonstrated efficacy in a live animal. Using an intraoperative probe we further demonstrated in vivo high wavenumber or fingerprint RS can distinguish cancer and normal brain tissue with >90% accuracy. Here we report on the design, development, and validation of a new intraoperative cancer detection optical needle system based on the combination of fingerprint and high wavenumber RS for highly accurate brain biopsy targeting based on molecular tissue features. This optical cancer detection device was engineered into the internal cannula of a widely used commercially available biopsy needle allowing tumor analysis prior to tissue harvesting with minimal workflow disruption. First in-human results are presented setting the stage for the clinical translation of this optical molecular imaging method for high yield and safe targeted brain biopsy.
Raman spectroscopy has been proven to have tremendous potential as biomedical analytical tool for spectroscopic disease diagnostics. The use of fiberoptic coupled Raman spectroscopy systems can enable in-vivo characterization of suspicious lesions. However, Raman spectroscopy has the drawback of rather long acquisition times of several hundreds of milliseconds which makes scanning of larger regions quite challenging. By combining Raman spectroscopy with a fast imaging technique this problem can be alleviate in part. Fluorescence lifetime imaging (FLIm) offers a great potential for such a combination. FLIm can allow for fast tissue area pre-segmentation and location of the points for Raman spectra acquisition. Here, we introduce an optical fiber probe combining FLIm and Raman spectroscopy with an outer diameter of 2 mm. Fluorescence is generated via excitation with a fiber laser at 355 nm. The fluorescence emission is spectrally resolved using a custom-made wavelength-selection module (WSM). The Raman excitation power at 785 nm was set to 50 mW for the in-vivo measurements to prevent sample drying. The lateral probe resolution was determined to be <250 μm for both modalities. This value was taken as step size for several raster scans of different tissue types which were conducted to show the overlap of both modalities under realistic conditions. Finally the probe was used for in vivo raster scans of a rat’s brain and subsequently to acquire FLIm guided Raman spectra of several tissues in and around the craniotomy.